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首页> 外文期刊>The EMBO journal. >Molecular basis for the bifunctional Uba4-Urm1 sulfur-relay system intRNAthiolation and ubiquitin-like conjugation
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Molecular basis for the bifunctional Uba4-Urm1 sulfur-relay system intRNAthiolation and ubiquitin-like conjugation

机译：双官能Uba4-Urm1的分子基础sulfur-relay系统intRNAthiolation和ubiquitin-like接合

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摘要

The chemical modification oftRNAbases by sulfur is crucial to tune translation and to optimize protein synthesis. In eukaryotes, the ubiquitin-related modifier 1 (Urm1) pathway is responsible for the synthesis of 2-thiolated wobble uridine (U-34). During the key step of the modification cascade, the E1-like activating enzyme ubiquitin-like protein activator 4 (Uba4) first adenylates and thiocarboxylates the C-terminus of its substrate Urm1. Subsequently, activated thiocarboxylated Urm1 (Urm1-COSH) can serve as a sulfur donor for specifictRNAthiolases or participate in ubiquitin-like conjugation reactions. Structural and mechanistic details of Uba4 and Urm1 have remained elusive but are key to understand the evolutionary branch point between ubiquitin-like proteins (UBL) and sulfur-relay systems. Here, we report the crystal structures of full-length Uba4 and its heterodimeric complex with its substrate Urm1. We show how the two domains of Uba4 orchestrate recognition, binding, and thiocarboxylation of the C-terminus of Urm1. Finally, we uncover how the catalytic domains of Uba4 communicate efficiently during the reaction cycle and identify a mechanism that enables Uba4 to protect itself against self-conjugation with its own product, namely activated Urm1-COSH.
机译：硫的化学改性oftRNAbases调整转换和优化的关键蛋白质合成。ubiquitin-related修饰符1 (Urm1)通路负责2-thiolated的合成摆动尿苷(U-34)。修改级联,E1-like激活激活酶ubiquitin-like蛋白4 (Uba4)腺苷酸和thiocarboxylates糖基的衬底Urm1。激活thiocarboxylated Urm1 (Urm1-COSH)作为一个为specifictRNAthiolases硫供体或参与ubiquitin-like接合反应。Uba4 Urm1仍然难以捉摸但是关键理解进化分支点ubiquitin-like蛋白质(UBL)之间sulfur-relay系统。长篇Uba4及其结构与衬底Urm1 heterodimeric复杂。展示Uba4编排的两个领域识别、绑定和thiocarboxylationUrm1的糖。的催化域Uba4沟通在反应周期和有效确定一个机制,使Uba4保护自己本身对self-conjugation产品,即Urm1-COSH激活。

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